Apparatus and method for producing a biocompatible three-dimensional object

ABSTRACT

An apparatus for making a biocompatible three-dimensional object including at least one delivery unit arranged to deliver at least one biocompatible fluid substance towards a 3D mold having a matrix surface to obtain a coating layer of a predetermined thickness configured for coating the matrix surface. The three-dimensional object may be a heart valve. Furthermore, a handling unit is provided arranged to provide a relative movement according to at least 3 degrees of freedom between the 3D mold and each delivery unit. The 3D mold is arranged to be coated by the delivered biocompatible fluid substance, in order to obtain a three-dimensional object having an object surface copying the matrix surface of the support body.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.14/838,205, filed Aug. 27, 2015, which is a continuation ofInternational Application No. PCT/IB2014/059291, filed Feb. 27, 2014,which claims priority to Italian Patent Application No. PI2013A000015,filed Mar. 7, 2013, each of which is incorporated by reference in theirentirety.

FIELD

The present disclosure relates to an apparatus for making abiocompatible three-dimensional object with complex shape, i.e. made oftwo or more surfaces presenting different radius of curvature. Inparticular, the present disclosure relates to the production of tissuesas well as biocompatible and blood-compatible membranes for makingvascular prostheses, concave or convex heart patches, ellipsoidalcardiac chambers, patches for calcaneal ulcers, or other components ofanatomical parts. The present disclosure relates also to a method formaking such three-dimensional objects.

BACKGROUND

As well known, many techniques and apparatus exist for making tissuesand biocompatible artificial membranes. In particular, the main knowntechniques provide the production of the above described artificialtissues by extrusion, or by spraying fluid substances. More in detail,the spraying techniques provide the deposit of a polymeric solution ofsynthetic origin by overlapping the polymeric solution in diluted formand a non-solvent, for example water, to each other. To this purpose asprayer is used which sprays both substances in an alternated way, or,alternatively, two sprayers are used that deliver the two substances atthe same time. The substances are deposited on a support body which hasthe same geometry of the desired tissue products or artificialmembranes.

An example of an apparatus for making such membranes by spraying isdisclosed in WO200405477. The apparatus uses a plurality of sprayers,each of them drawing from a respective reserve a component of thebiological mixture. A cylindrical support element is then arranged onwhich the fluid substances supplied by the sprayers are deposited, inorder to make a coating that forms the desired membranes. Thecylindrical support element can kinematically rotate about a fixedrotation axis, whereas the sprayers are moved by a carriage that makes atranslational movement along an axis that is substantially parallel tothe rotation axis of the cylindrical support element. This way, thefluid substances supplied can deposit on the whole surface of thesupport element.

However, this solution, as it can be understood, is applicable only incase the membranes to make have a relatively simple and regular shapewith surfaces presenting a wide radius of curvature and not too suddenlyvariable. Such membranes should also have substantially axisymmetricshape, in order to keep a constant spraying flow during the rotation ofthe support element.

A similar apparatus is disclosed in WO2010136983. Even in this case, theapparatus is used for making a biocompatible structure that allowsregenerating biological tissues with simple shape. Notwithstanding theabove, the apparatus as above described for making tissues orbiocompatible artificial membranes cannot provide anatomical. prostheseswith complex shape, such as concave or convex heart patches, ellipsoidalcardiac chambers, patches for calcaneal ulcers, or portions of organs.

U.S. Pat. No. 5,376,117 describes a breast prosthesis for subcutaneousimplants. The prosthesis consists of an outer shell comprising anon-porous layer of biocompatible polymeric material and a porous outerlayer that coat wraps the non-porous layer. The outer layer is made byelectrostatic deposit of biocompatible polymeric fibers on the innerlayer. Once obtained the three-dimensional structure, the prosthesis isoverturned and arranged on a spindle that is rotated about its own axis,in order to make the convex side of the prosthesis.

A breast prosthesis obtained by a process similar to that described inU.S. Pat. No. 5,376,117 is disclosed also in WO2010/059834. However,both processes, as described in U.S. Pat. No. 5,376,117 andWO2010/059834, are not suitable for the production of tissues andbiocompatible artificial membranes with complex shape and with smalltolerances, since they cannot ensure an accurate definition of themodelled forms.

SUMMARY

Existing limitations associated with the foregoing, as well as otherlimitations, can be overcome by an apparatus for and method forproducing a biocompatible object. Briefly, and in general terms, thepresent disclosure is directed to various embodiments of an apparatusfor and method for producing a biocompatible object.

In general terms, the present disclosure provides an apparatus thatallows the production of a biocompatible three-dimensional object withcomplex shape, i.e. not necessarily equipped with significant symmetriesand, in particular with surfaces having different radius of curvature.The present disclosure may also provide an apparatus that allows for theproduction of such three-dimensional object with high dimensionalprecision, in order to copy accurately a pre-designed model.

Further, the present disclosure may provide an apparatus that allowsprogramming the whole production work so that it can be carried out inan automatic way.

Briefly, and in general terms, the present disclosure is directed to anapparatus for making a biocompatible three-dimensional object. Theapparatus includes at least one delivery unit arranged to deliver atleast one biocompatible fluid substance towards a support body, alsocalled core, that has a matrix surface, to obtain a coating layer of apredetermined thickness configured for coating the matrix surface. Thebiocompatible fluid substance may include a plurality of particles. Theapparatus also includes a handling unit for determining a relativemovement according to at least 3 degrees of freedom between the supportbody and the delivery unit. This is so that the support body may becoated with the delivered biocompatible fluid substance to obtain athree-dimensional object having an object surface copying the matrixsurface of the support body. Further, the apparatus includes a suctionand blowing unit is also provided configured to provide a suction andblowing current arranged to remove from the support body any surplusparticles of the biocompatible fluid substance supplied by the or eachdelivery unit. In this example, it is possible to deposit a uniformpredetermined thickness of coating layer on the matrix surface. Thesolution provided by the present disclosure, and in particular thepossibility of actuating relatively the support body and the deliveryunit according to at least 3 degrees of freedom during the coating stepsof the matrix surface, makes it possible to control with high precisionthe deposit of the biocompatible fluid substance on the matrix surface.It is also possible to adjust, in a correspondingly precise way and asit is needed, the thickness of the layers of deposited fluid substance.This is possible since the handling unit is capable to expose the matrixsurfaces of the support body to a jet of biocompatible fluid substancesupplied by the delivery unit, positioning this matrix surfacesubstantially orthogonally to the jet.

After the deposit of the fluid substances, the coating is removed fromthe support body giving rise to the sought three-dimensional object.

In certain embodiments, the handling unit is arranged to provide arelative movement according to 4 degrees of freedom, advantageously,according to 5 degrees of freedom, preferably according to 6 degrees offreedom. In one embodiment, the handling unit includes ananthropomorphic robot having a chain of pivot joints that has an endconnected to a fixed base and the other end connected to a support baseto which the support body, and/or the delivery unit, can be mounted in aremovable way. Such chain of pivot joints is adapted to actuate thesupport body, and/or the delivery unit, according to at least 6 degreesof freedom, supplying higher design precision in generating the soughtthree-dimensional object.

Alternatively, the handling unit may include a plurality of actuators,each of which has one end engaged with a fixed base and another endengaged with a support base to which the support body, and/or thedelivery unit, can be mounted in a removable way.

In certain embodiments, the actuators may be pneumatic actuators,hydraulic actuators, electric actuators, or a combination thereof.

In one embodiment, the suction and blowing unit may be replaced with asuction device, or the suction and blowing unit may include a suctiondevice and a blowing device. The suction device may be a fixed suctiondevice. Alternatively, the suction device can be a movable suctiondevice associated with auxiliary moving means arranged to move thesuction device, in order to follow spatially the position of the supportbody during its handling by the handling unit. This way, any surplusparticles of the biocompatible fluid substance can be removed regardlessof the position of the support body.

In a further exemplary embodiment, the suction device may include asuction hood integral to the support base and configured to surroundlaterally the support body, in order to maximize the suction of anysurplus particles of the biocompatible fluid substance. A suction tubemay also be included which is arranged to connect pneumatically thesuction hood with a suction system. This way, it is not necessary theimplementation of the auxiliary moving means, since the hood is in anoptimal position for suction of any surplus particles of thebiocompatible fluid substance, whichever is the position of the supportbody. In one embodiment, the hood may have a toroidal, cylindrical, ortubular shape.

In one embodiment, the suction device may include a storage reservoir ofany surplus particles or a filter on which such particles can deposit.Furthermore, the suction or blowing current from the suction and blowingunit can be generated by a fan or a compressor located upstream of thesuction tube.

In one example, the apparatus may include a first delivery unit arrangedto deliver a first jet of a first biocompatible fluid substance towardsthe support body. The first biocompatible fluid substance being abiomaterial of synthetic origin. The apparatus of this embodiment alsomay include a second delivery unit arranged to deliver a second jet of asecond biocompatible fluid substance towards the support body. Thesecond biocompatible fluid substance being a non-solvent, for example,water. The second delivery unit is arranged to direct the seconddelivery jet towards the support body, in order to overlap the seconddelivery jet to the first delivery jet. This may induce a quick depositof the synthetic biomaterial supplied onto the support body by the firstdelivery unit, obtaining a filamentous three-dimensional structure.

In yet another embodiment, the apparatus also includes a counter-mold.The counter-mold may be adapted, once ended the delivery of thebiocompatible fluid substances, to press, in particular to heat, thecoating layer that is deposited on the support body. This is to obtain abetter finishing of the shape of the three-dimensional object, inaddition to improved mechanical features.

In another embodiment, the apparatus also includes third delivery unitarranged to deliver a third biocompatible fluid substance, in particulardiluted in solution, both of synthetic and biological origin. In certainembodiments with two or three delivery units, with respective deliveryof jets of biocompatible fluid substances, there may be a program meansconfigured for combining the alternation of such delivery. This way, thestep of coating can be completely automated, and does not require, innormal conditions, manual monitoring.

Also, in one embodiment, a control means is also provided for monitoringthe thickness of the formed coating layer, in order to test that thecoating layer has thickness corresponding to that of the designedcoating layer. In particular, the designed coating layer can be providedto apparatus by a control CAD.

The current disclosure is also directed to a method for making abiocompatible three-dimensional object. The method includes the step ofdelivery of at least one biocompatible fluid substance towards a supportbody, also called core, which has a matrix surface. Also, the methodincludes obtaining a coating layer of predetermined thickness configuredfor coating the matrix surface. The delivery occurring using at leastone delivery unit. The method also includes handling the support bodyand/or the delivery unit with a handling unit, in order to provide arelative movement according to at least 3 degrees of freedom between thesupport body and the delivery unit. This is so that the support body iscoated with the delivered biocompatible fluid substance to obtain athree-dimensional object having an object surface copying the matrixsurface. There may be multiple delivery units and the at least 3 degreesof freedom may be between the support body and each of the deliveryunits. The method also includes removing from the support body anysurplus particles of the biocompatible fluid substance dispensed with asuction and blowing unit. The removing being carried out through asuction or a blowing step, in order to make uniform the predeterminedthickness of the coating layer. The suction and blowing unit may bereplaced with a suction device or a blowing device.

Further, the current disclosure discloses a method to produce abiocompatible three-dimensional heart valve. The method includes thestep of determining a size and geometry of the heart valve andproducing, using a computer processor, a virtual three-dimensional modelof the heart valve based on the predetermined size and geometry. Themethod also includes creating a three-dimensional mold and a countermold of the virtual three-dimensional model of the heart valve andspraying a layer of a biocompatible polymeric resin on the surface ofthe three-dimensional mold. A stent may also be disposed on the mold andcovered with a layer of biocompatible polymeric resin. The methodfurther includes pressing the counter mold on the biocompatiblepolymeric resin layer covered surface of the three-dimensional mold andallowing the biocompatible polymeric resin layer to cure and dry insitu. The method also includes extracting the dry biocompatiblepolymeric resin layer covered three-dimensional mold from the countermold and removing the dry biocompatible polymeric resin layer from thethree-dimensional mold.

In one embodiment, the size of the heart valve is determined bydifferent scanning techniques, for example, CT, FL, DR and MRI. Inanother embodiment, the geometrical design of the heart valve is one ofnarrow orifice, symmetrical leaflets or asymmetrical leaflets. In yetanother embodiment, the three-dimensional mold and the counter mold ofthe virtual three-dimensional model of the heart valve are created usinga rapid prototyping process, for example, vacuum casting.

Other features and advantages will become apparent from the followingdetailed description, taken in conjunction with the accompanyingdrawings, which illustrate by way of example, the features of thevarious embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure will be now shown with the following descriptionof some exemplary embodiments thereof, exemplifying but not limitative,with reference to the attached drawings in which:

FIG. 1 shows an exemplary embodiment of an apparatus including ananthropomorphic robot arranged to handle the support body;

FIG. 2 shows an exemplary embodiment of an apparatus, which differs fromthat of FIG. 1 for the presence of a toroidal hood arranged to surroundthe support body;

FIG. 3 shows an exemplary embodiment of the apparatus, which differsfrom that of FIG. 2 since the handling unit the support body does notinclude an anthropomorphic robot, but a plurality of linear actuators;

FIG. 4 shows a counter-mold that allows a hot molding of the coatinglayer;

FIG. 5 shows a three-dimensional object resulting from the productionprocess;

FIG. 6A shows a cardiac chamber with a heart patch applied to it; and

FIG. 6B shows a support from which the heart patch of FIG. 6A isgenerated.

FIG. 7 shows an example of workstation for a three-dimensional sprayingsystem including the anthropomorphic robot;

FIGS. 8A and 8B show an exemplary embodiment of an apparatus includingan anthropomorphic robot arranged to handle a 3D mold of a heart valveand an exploded view of the 3D mold;

FIG. 9 shows a flow chart for one embodiment of a method for creating a3D heart valve;

FIGS. 10A and 10B show an example of a heart valve having asymmetricleaflets;

FIGS. 11A and 11B show an example of a heart valve having a narroworifice;

FIGS. 12A and 12B show an example of a heart valve having symmetricleaflets;

FIGS. 13A and 13B show an one example of an exploded view of a heartvalve and stent on a mold and inserted into a mandrel for pressing acounter-mold against the heart valve on the mold.

DETAILED DESCRIPTION

Each of the features and teachings disclosed herein can be utilizedseparately or in conjunction with other features and teachings toprovide an apparatus for and method for producing a biocompatibleobject. Representative examples utilizing many of these additionalfeatures and teachings, both separately and in combination are describedin further detail with reference to the attached figures. This detaileddescription is merely intended to teach a person of skill in the artfurther details for practicing aspects of the present teachings and isnot intended to limit the scope of the claims. Therefore, combinationsof features disclosed above in the detailed description may not benecessary to practice the teachings in the broadest sense, and areinstead taught merely to describe particularly representative examplesof the present teachings.

In the description below, for purposes of explanation only, specificnomenclature is set forth to provide a thorough understanding of thepresent disclosure. However, it will be apparent to one skilled in theart that each of these specific details are not required to practice theteachings of the present disclosure.

Moreover, the various features of the representative examples may becombined in ways that are not specifically and explicitly enumerated inorder to provide additional useful embodiments of the present teachings.It is also expressly noted that all value ranges or indications ofgroups of entities disclose every possible intermediate value orintermediate entity for the purpose of original disclosure. It is alsoexpressly noted that the dimensions and the shapes of the componentsshown in the figures are designed to help to understand how the presentteachings are practiced, but not intended to limit the dimensions andthe shapes shown in the examples. In this document, measurements,values, shapes, angles, and geometric references (such asperpendicularity and parallelism), when associated with words like“about” or other similar terms such as “approximately” or“substantially,” should be construed to allow for measurement errors orothers errors due to production and/or manufacture process, and may varyby up to ten percent.

With reference to FIG. 1, an exemplary embodiment of an apparatus 100for making a biocompatible three-dimensional object 30 provides ananthropomorphic robot 132 having a kinematical chain of pivot joints133. Such chain of joints 133 is constrained at an end to a fixed base134, and at another end to a support base 131 on which support body 20engages in a removable way. The chain of pivot joints 133 of FIG. 1allows handling the support body according to six degrees of freedom,allowing an optimum precision when generating the soughtthree-dimensional object 30.

In FIG. 1, three delivery units 110,111,112 are shown that are arrangedto deliver three different biocompatible fluid substances. Fewer or moredelivery units can be arranged to deliver biocompatible fluidsubstances. In particular, first delivery unit 110 is adapted to delivera jet of a biomaterial of synthetic origin towards the support body 20.The second delivery unit 111 is, instead, arranged to deliver a jet ofnon-solvent, for example water, overlapping to the jet generated byfirst delivery unit 110, in order to induce a quick deposit of thebiopolymeric material supplied onto support body 20 by first deliveryunit 110, allowing to obtain a filamentous three-dimensional structure.The third delivery unit, finally, is adapted to deliver a thirdbiocompatible fluid substance diluted in solution, in particular anotherbiomaterial of synthetic or biological origin.

Each delivery unit 110,111,112 also has a hydraulic circuit (not shownin the figure, for example, a cylinder-piston mechanism) consisting ofducts, with possible valves and pumps, which connect the or eachdelivery unit to reservoirs containing the biocompatible fluidsubstances.

In this exemplary embodiment, a suction and/or blowing unit 120 isfurther provided, adapted to generate a suction and/or blowing current.This way, the suction and/or blowing unit 120 makes it possible to levelthe thickness of the coating layer 35 and to remove from support body 20any surplus particles of the biocompatible fluid substances supplied bythe or each delivery unit 110, 111, 112. The device 120 is alsospatially moved by auxiliary moving means 140, in such a way that thisdevice 120 can follow spatially the position of support body 20 duringits handling steps by handling unit 130. In some embodiments, the base134 of the handling unit 130 can be automated or free such that it iscontrolled by a user. Moreover, the structure of the handling unit 130is not limited to the structure shown in the figures.

In FIG. 2 a second exemplary embodiment is shown, which differs from anexemplary embodiment of FIG. 1 as from the type of the device 120. Inthis exemplary embodiment, device 120 includes a toroidal suction hood121, which is integral to support base 131 and is configured to surroundlaterally support body 20. Toroidal hood 121 is then joined to a suctiontube 122 arranged in turn to connect pneumatically the suction hood 121with a suction system 123 that has a compressor to generate a suctionflow and with a storage reservoir containing any surplus particles ofthe dispensed fluid substance.

Alternatively, in an exemplary embodiment not shown in the figures,device 120 is a blowing device including a compressor adapted togenerate a blowing current for removing any surplus particles of thedelivered fluid substance. This way, it is not necessary that theapparatus includes auxiliary handling unit 140, like the exemplaryembodiment of FIG. 1, since the toroidal hood 121 surrounds laterallythe support body 20, whichever is the position reached by handling unit130. However, in some embodiments, any surplus particles of thedelivered fluid substance can be removed by laser or other abradingmethod.

In FIG. 3 an exemplary embodiment is shown where handling unit 130,instead of including the anthropomorphic robot 132 of the previousfigures, includes a plurality of linear actuators 133, each of whichengages, at one end, to fixed base 134, and at another end, to supportbase 131. Support body 20 engages in a removable way with support base131, like the previous exemplary embodiments. The handling unit canreach the same degrees of freedom of an anthropomorphic robot, even ifwith narrower handling range. The advantage offered by this solution isshown by a high reduction of the encumbrance.

In FIG. 4 the step is shown of pressing, in particular to hot pressing,of the coating layer 35 deposited by the or each delivery unit110,111,112, using a counter-mold 150. The coating layer 35 is thenremoved from support body 20 and becomes substantially the finalbiocompatible three-dimensional object 30, visible in FIG. 5.

Owing to the hot pressing an optimum finishing of the shape of thethree-dimensional object 30 can be achieved, in such a way that suchshape is closest to the designed patch shape, for example provided byCAD or the like. Such pressing operation also gives to thethree-dimensional object 30 mechanical improved features, reaching anydesign standards.

The apparatus 100, as described above, and shown in FIGS. 1 to 5,provides biocompatible three-dimensional objects 30 of whichever shape.In particular, biocompatible three-dimensional objects 30 can bemanufactured both of simple and regular shape, such as a tetrahedron ora cone, and of irregular shape and/or with surfaces which cannot workedout in a simple way, such as a concave or convex patch or an ellipsoidalpatch. Furthermore, biocompatible three-dimensional objects 30 can beprovided having surfaces with different radius of curvature and/or withdifferent angles.

In FIG. 6A a cardiac chamber of a human heart is shown to which abiocompatible three-dimensional object 30 is mounted, in particular aheart patch, consisting of an inner portion 30 a and an external portion30 b.

In FIG. 6B part of the apparatus 100 including the support 20 is shown,from which the inner portion 30 a of the heart patch of FIG. 6A isgenerated.

By way of example only, and not by way of limitation, a system forcreating a heart valve will now be described. In one embodiment, FIG. 7discloses a system 700 for making a synthetic, biocompatiblethree-dimensional (3D) heart valve 701 (shown in FIG. 13A). The system700 includes an anthropomorphic robot 132 (e.g.; ABB IRB 120 industrialrobot or the like), as described above, stationed on a workbench 712.The system also includes a 3D mold 702 mounted on a support body 20. Inthis example, the 3D mold 702 is for a heart valve, however, the moldmaybe shaped to design for any other object. The anthropomorphic robot132 also includes a chuck 131 to releasably hold the support body 20 andthe 3D mold 702. Two spray guns 110 and 111, as described above, arealso shown disposed on the workbench 712. However, a person skilled inthe art can appreciate that a plurality of spray guns can be useddepending on the desired heart valve structure. By way of example only,and not be way of limitation, the system may have up to 10 deliveryunits or spray guns. Also attached to the workbench 712 are twocontinuous pumps 704 and an air compressor 705. A chemical container 706is also shown, and the chemical container 706 may store one or morebiocompatible fluid substances, to be sprayed on the 3D mold 702. Incertain embodiments, multiple containers may be used to store differentbiocompatible substances to be sprayed through one or both of the sprayguns 110 and 111. The chemical container 706 is attached to one or bothof the two continuous pumps 704. An electronic control unit 707 may bedisposed on or near the workbench 712 and be in communication with theanthropomorphic robot 132. In one embodiment, the electronic controlunit 707 may supply power and operating instructions to theanthropomorphic robot 132, pumps 704, air compressor 705, and/or sprayguns 110 and 111. A suction and/or blowing unit 120 (not shown in FIG.7) may also be provided with the system 700.

FIG. 8A discloses a close up view of the top section of the system 700including the anthropomorphic robot 132, the 3D mold 702, two spray guns110 and 111, and a suction and/or blowing unit 120. As mentioned above,the anthropomorphic robot 132 includes a kinematical chain of pivotjoints 133. Such chain of joints 133 is constrained at an end to a fixedbase 134, and at another end to a support base 131 on which support body20 engages in a removable way. The support base 131 may be a chuck incertain embodiments. The chain of pivot joints 133 allows handling ofthe support body according to six degrees of freedom, which in turnallows an optimum precision when generating the sought 3D heart valve701.

Moreover, as shown in FIG. 8A, two delivery units 110,111 of a sprayinggroup are arranged to deliver two different biocompatible fluidsubstances. In particular, first delivery unit 110 is adapted to delivera jet of a biomaterial of synthetic origin towards the 3D mold 702 inthe same manner as described above with reference to spray coating thesupport body 20. The second delivery unit 111 is arranged to deliver ajet of non-solvent, for example, water, overlapping to the jet generatedby the first delivery unit 110 in order to induce a quick deposit of thebiopolymeric material supplied onto 3D mold 702 by the first deliveryunit 110. Subsequently, obtaining a filamentous 3D structure of thedesired heart valve 701.

FIG. 8A also shows a suction and/or blowing unit 120 to generate suctionand/or blowing current. By using the suction and/or blowing unit 120 thethickness of a coating layer on the 3D mold 702 can be levelled andsurplus particles of the biocompatible fluid substances supplied by theeach delivery unit 110 and 111 can be removed from support body 20. Inone embodiment, the delivery units 110 and 111 are equipped with a 90degree end axis in order to check the spraying process over a 3D valveshape. The delivery units 110 and 111 may move about an axis during thespraying process to create the 3D valve shape. FIG. 8B shows an explodedview of the 3D mold.

As described above, the suction and/or blowing unit 120 is alsospatially moved by auxiliary moving means 140, in such a way that thisdevice 120 can follow spatially the position of 3D mold 702 during itshandling steps by handling unit 130 (also as described above). In someembodiments, the suction and/or blowing unit 120 can host a removableplatform for maintenance aims.

According to one embodiment, FIG. 9 discloses a method 900 to make thesynthetic, biocompatible 3D heart valve 701 of this example using theanthropomorphic robot 133. In one embodiment, the anthropomorphic robotmay have three to six degrees of freedom.

At the first step 901 of the method 900, a proper size and geometry ofthe heart valve 701 of the prospective patient is determined. In oneembodiment, sizing the heart valve 701 is achieved by scanning (e.g.;via CT, FL, DR, MRI and the like) or visually inspecting theimplantation site (i.e.; prospective patient's heart). The geometry ofthe heart valve is selected based on the desired characteristic of theheart valve 701 (shown in FIG. 13A). Such geometry may differ dependingon the size and condition of the heart of the patient. For example, asshown in FIGS. 10A-10B, a heart valve 701 with asymmetrical leafletsgeometry may be chosen. Such design geometry may offer improved valvularclosure capability and may preserve opening efficiency. However, othergeometrical designs (e.g. narrow orifice, symmetrical leaflets or thelike) can be chosen for the heart valve 701 as well, depending on thedesired characteristic. For example, as shown in FIGS. 11A-11B, a heartvalve with a narrow orifice 1101 geometry may be chosen, which offersbiocompatible design, simple leaflets geometry and good closurecapability. On the other hand, as shown in FIGS. 12A-12B, a heart valvewith a symmetrical leaflets design 1201 may be chosen, which may offerimproved valve opening, since the warps in this design increases thesurface of each leaflets. It should be understood that various designsmay be chosen for the heart valve depending on the desiredcharacteristics for the patient.

Once the proper size and geometry of the desired heart valve 701 isdetermined, at the next step 902, a virtual 3D model 708 of the heartvalve 701 is digitally produced. Although a 3D model 708 of the desiredheart valve may be created by hand or other machinery, it is preferredto create a virtual 3D model 708 of the heart valve. In one embodiment,the virtual 3D model 708 may be created using 3D computer-aided design(CAD) software.

At the next step 903, a 3D mold 702 and a counter mold 709 (FIG. 13B)may be created from the virtual 3D model 708. Different techniques, forexample, 3D rapid prototyping process, vacuum casting, 3D printing, orthe like, can be used to create the 3D mold 702 and the counter mold709. In some embodiments, the mold and the counter mold can be made ofsteel to improve the quality of the 3D heart valve architecture.

In some embodiments, a stent 710 can be placed on the 3D mold 702, inorder to incorporate the stent into the inner walls of the 3D heartvalve 701. A stent 710 incorporated with the heart valve 701 is bestshown in the exploded view of FIG. 13A. The stent 710 can beincorporated into the heart valve 701 by forming a coating around thestent 710 and the 3D mold 702 during the spraying process to form theheart valve 701. In other embodiments, the stent 710 can be incorporatedinto the heart valve 701 after the heart valve 701 is created. This maybe done by attaching the stent 710 inside or around the exterior surfaceof the heart valve 701. A stent 710 maintains the cross-sectional shapeof the 3D heart valve 701 and can help secure the 3D heart valve 701within the patient, e.g., by suturing the stent and valve in positionwithin the patient. As shown in the figures, the cross-sectional shapeof the heart valve is generally circular in shape at one end, howeverthe cross sectional shape of the heart valve may take on other shapes.Stents usually are made of metal mesh, but sometimes they can be made offabric.

Next at step 904, a biocompatible fluid substance is sprayed onto the 3Dmold 702 in order to deposit the biocompatible fluid substance on thesurface of the 3D mold 702, and in certain embodiments, on the surfaceof a stent 710 too. The spraying of the biocompatible fluid substanceonto the 3D mold 702 is shown in FIGS. 7 and 8. In this embodiment,different biocompatible fluids, for example, biocompatible polymericresin, elastomer biomaterial, polyurethane, silicone based fluids, orthe like can be used depending on the desired characteristics of theheart valve 701.

Once the spraying step is complete, at the next step 905, as shown inFIG. 13A, the 3D mold 702 including the coating forming the heart valve701, and the stent 710 in certain embodiments, is removed from the chuck131 of the robot 132 and is inserted in a mandrel 714 including thecounter mold 709. The mandrel 714 will accept the mold 702 in a recess.

Once inserted into the mandrel 714, at step 906, jaws 713 of the countermold 709 are moved from the edge of the mandrel 714 towards the 3D mold702 via the slots 711 of the mandrel 714 and pressed against the newlycreated valve on the 3D mold 702. The jaws 713 of the counter mold 709can be moved towards the 3D mold 702 via the slots 711 manually orautomatically. The design of the counter mold 709 can help to obtain abetter surface quality and reduced porosity of the 3D heart valve 701.Additionally, as mentioned above, in some embodiments, hot pressing canbe used to achieve an optimum finishing of the shape of the 3D heartvalve 701, in such a way that such shape is closest to the 3D mold 702.Hot pressing also improves the mechanical features of the 3D valve 701.

Next, at step 907, the biocompatible fluid substance on the 3D mold 702is cured. In one embodiment, the 3D mold may be cured in an oven between70° and 90° Celsius for approximately 20 to 40 minutes. It is known thatthe temperature and time for curing in an oven could vary depending onthe type of biocompatible fluid substance being used to form the 3D mold702. The newly created heart valve 701 can be allowed to cool in situ.In another embodiment, the 3D mold may be cured without using an oven,for example, by cold curing the 3D mold with chemicals or other process.

After the spraying and curing processes, a portion of the mold the mayextend past the ends (top side) of the jaws 713 of the counter mold 709.Before or after the curing process, preferably after the curing process,the portion of the mold extending past the jaws 713 is cut in order toform and obtain the desired shape of the valve leaflets. This cut of themold affects the end portion (distal end) of the valve leaflets. In oneembodiment, the cut to form the distal end of the leaflets is made witha blade, such as a scalpel. Also, the cut may be made with a robotic armor machine using a blade, and in certain embodiments, the cut may bemade manually. It has also been contemplated that a laser may be used tocut the distal end of the leaflets. The laser may be manually controlledor controlled by a machine or robotic arm.

Once the curing is complete, at step 908, the dry biocompatible fluidsubstance layer coated 3D mold 702, and stent in certain embodiments, onthe support body 20 is extracted from the counter mold 709. The drybiocompatible fluid substance layer on the 3D mold 702 becomes finalbiocompatible 3D heart valve 701. Next, at step 909, the newly created3D heart valve 701 is sterilized. The newly created 3D heart valve 701includes the dried biocompatible fluid substance layer, and stent incertain embodiments. The valve 701 may be sterilized by wet or steamsterilization, dry heat sterilization, ethylene oxide, sporicidalchemicals, glass plasma, irradiation (gamma rays), or the like.

Next, at step 910, a surgeon may implant the 3D heart valve 701,including the stent in certain embodiments, in the heart of the patient.The synthetic heart valve 701 produced using the method 900, is costeffective, biocompatible, rapidly manufactured, highly customizable, anddurable.

In some embodiments, the heart valve 701 can be produced directly fromthe 3D model 708, via 3D printing, CNC machining, or other methods.However, while typical production process might take several days, thespraying technique, as described in FIG. 9, for a singular valve can becompleted less than 30-40 minutes. In addition to the increased speed ofproduction, valves produced by the 3D spraying technique have very highbiocompatibility and strong structural resistance. Therefore, theproduction process 900, as disclosed herein, dramatically decreasescosts and permits easy production of variable sizes and geometries,making it suitable for veterinary use. This makes the process 900 idealto for the application that requires low implant cost and greatdimensional to accommodate the greatly varying valves of differentspecies of animal. However, a person skilled in the art can appreciatethat a prosthetic 3D human heart valve can also be produced using theprocess 900. It should also be appreciated that any type of prostheticheart valve, such as a single leaflet valve, bileaflet valve, tiltingdisc valve, cage and ball valve, bicuspid valve, a mechanical valve, orthe like may be used.

The foregoing description of specific exemplary embodiments will sofully reveal the invention according to the conceptual point of view, sothat others, by applying current knowledge, will be able to modifyand/or adapt in various applications the specific exemplary embodimentswithout further research and without parting from the invention, and,accordingly, it is meant that such adaptations and modifications willhave to be considered as equivalent to the specific embodiments. Themeans and the materials to realize the different functions describedherein could have a different nature without, for this reason, departingfrom the field of the invention, it is to be understood that thephraseology or terminology that is employed herein is for the purpose ofdescription and not of limitation.

What is claimed:
 1. A method for making a biocompatiblethree-dimensional heart valve, the method comprising the steps of:delivering at least one biocompatible fluid substance towards a moldhaving a mold surface to obtain a coating layer of predeterminedthickness configured for coating the mold surface, using at least onedelivery unit, the biocompatible fluid substance including a pluralityof particles; handling with a handling unit the mold and the deliveryunit in order to provide a relative movement with at least three degreesof freedom between the mold and the delivery unit, the mold coated withthe at least one biocompatible fluid substance that is delivered toobtain a three-dimensional heart valve having a surface corresponding tothe mold surface; removing from the mold any surplus particles of the atleast one biocompatible fluid substance dispensed using a suction andblowing device in order to make uniform the predetermined thickness ofthe coating layer; and pressing a counter mold on the coating layerdeposited on the mold after delivering the biocompatible fluidsubstance.
 2. The method of claim 1, further comprising determining asize and geometry of the heart valve.
 3. The method of claim 2, whereindetermining the size of the heart valve is achieved by scanning.
 4. Themethod of claim 3, wherein the scanning is selected from the groupconsisting of CT, FL, DR and MRI.
 5. The method of claim 2, wherein thegeometry of the heart valve is selected from the group consisting ofnarrow orifice, symmetrical leaflets and asymmetrical leaflets.
 6. Themethod of claim 2, further comprising producing, using a computerprocessor, a virtual three-dimensional model of the heart valve.
 7. Themethod of claim 6, further comprising creating the mold and the countermold based on the virtual three-dimensional model of the heart valve. 8.The method of claim 1, wherein the at least one biocompatible fluidsubstance is selected from the group consisting of biocompatiblepolymeric resin, elastomer biomaterial, polyurethane, and silicone. 9.The method of claim 1, further comprising curing and drying the moldcoated with the at least one biocompatible fluid substance in situ. 10.The method of claim 9, further comprising sterilizing the dry moldcoated with the at least one biocompatible fluid substance.
 11. Themethod of claim 10, further comprising extracting the dry mold coatedwith the at least one biocompatible fluid substance from the countermold.
 12. The method of claim 11, further comprising removing a drylayer of the biocompatible fluid substance from the mold.
 13. The methodof claim 1, wherein a plurality of biocompatible fluid substances aredelivered towards mold using a plurality of delivery units.
 14. Themethod of claim 1, wherein the heart valve is chosen from a groupconsisting of a bicuspid valve, single leaflet valve, bileaflet valve,cage and ball valve, and titling disc valve.
 15. A system for making abiocompatible three-dimensional heart valve, the system comprising: atleast one delivery unit configured to deliver at least one biocompatiblefluid substance towards a mold having a mold surface to obtain a coatinglayer of predetermined thickness configured for coating the moldsurface, the biocompatible fluid substance having a plurality ofparticles; a handling unit configured to provide a relative movementwith at least three degrees of freedom between the mold and the deliveryunit, wherein the mold is coated with the at least one biocompatiblefluid substance that is delivered to obtain a three-dimensional heartvalve having a surface corresponding to the mold surface; and a suctionand blowing device configured to generate a suction and blowing current,wherein the suction and blowing current removes from the mold anysurplus particles of the biocompatible fluid substance supplied by thedelivery unit.
 16. The system of claim 15, wherein the handling unitincludes an anthropomorphic robot having a chain of pivot joints, thechain of pivot joints having a first end connected to a fixed base and asecond end connected to a support base to which the mold is mounted in aremovable way, the chain of pivot joints arranged to move the mold,according to at least 6 degrees of freedom.
 17. The system of claim 15,wherein the handling unit includes a plurality of linear actuators, eachactuator of the plurality having a first end engaged with a fixed baseand a second end engaged with a support base to which the mold ismounted in a removable way.
 18. The system of claim 15, wherein thesuction and blowing device is fixed.
 19. The system of claim 15, whereinthe suction and blowing device is movable and associated with a motorarranged to move the suction and blowing device, the motor beingconfigured to allow the suction and blowing device to follow spatiallythe position of the mold during its handling by the handling unit. 20.The system of claim 15, wherein the suction and blowing device includesa suction hood integral to the support base and configured to surroundlaterally the mold to maximize the suction of the surplus particles ofthe biocompatible fluid substance, and a suction tube arranged toconnect pneumatically the suction hood with a suction system to generatea suction flow.
 21. The system of claim 15, wherein the at least onedelivery unit includes a first delivery unit arranged to deliver a firstjet of a first biocompatible fluid substance towards the mold, the firstbiocompatible fluid substance being a biomaterial of synthetic origin,and a second delivery unit arranged to deliver a second jet of a secondbiocompatible fluid substance towards the mold, the second biocompatiblefluid substance being a non-solvent, the second delivery unit arrangedto direct the second delivery jet towards the mold in such a way thatthe second delivery jet is overlapped to the first delivery jet,inducing a quick deposit of the synthetic biomaterial supplied onto themold from the first delivery unit obtaining a filamentousthree-dimensional structure.
 22. The system of claim 21, wherein thesecond biocompatible fluid substance is water.
 23. The system of claim15, further comprising a counter-mold that is adapted to press thecoating layer deposited on the mold.
 24. The system of claim 21, whereinthe at least one delivery unit further includes a plurality of deliveryunits arranged to deliver a plurality of biocompatible fluid substances.25. The system of claim 24, wherein the plurality of biocompatible fluidsubstance includes a biopolymeric material of synthetic origin.
 26. Thesystem of claim 15, where the mold is three-dimensional.
 27. The systemof claim 16, further comprising at least one air compressor and at leastone chemical container in communication with the delivery unit.
 28. Thesystem of claim 27, further comprising one or more continuous pumpsattached to the fixed base, wherein the one or more continuous pumpsdeliver fluids from the chemical container to the delivery unit.
 29. Thesystem of claim 28, further comprising an electronic control unit incommunication with the anthropomorphic robot, the electronic controlunit supplies power and operating instructions to the anthropomorphicrobot, continuous pumps, air compressor and the delivery unit.